Pain in biologically immature neonates induces numerous physiologic, endocrine, and behavioral changes that potentially have anegative imapce on long term neuro-developemental functioning. Medical care of infants born at very low gestational age involves systematic repeated exposure to noxious procedures, which induce stress and pain. Knowledge of the developmental course of pain reactivity in VLGA (<30 weeks) infants is urgently needed. We propose to study the neonatal development of early multidimensional pain responses of VLGA infants. The specific aims are to 1) determine the immediate and subsequent effects of pharmacologic treatment on pain responses and developmental outcomes; 2) distinguish pain from stress in VLGA infants; 3) examine the role of neurologic lesion in the early development of altered pain response in infants with SNI; 4) examine whether early postnatal pain experience may result in ongoing hyperarousal; and 5) examine the effect of early and prolonged pain experience on subsequent neurobehavioral development during infancy. Biobehavioral pain and stress responses will be studied in VLGA infants randomized to either sedation or analgesia treatment groups, an in those not requiring sedation or analgesia. Pain responses will be measured on days 5 and 14, and at 32 weeks PCA. A multivariate approach to examining behavioral (facial and body actions) and physiological (spectral analysis of heart rate, oxygen saturation, cortisol) responses to pain and stress events will be used. Neurodevelopmental functioning will be assessed in follow-up at 3, 6, 8, and 18 months CCA. The results of these studies will have both theoretical importance and significant implications for clinical management of pain in VLGA infants.